There is an increasing demand for effective natural, non-toxic therapeutic agents to treat or prevent diseases, improve human health and promote longevity. Trans-resveratrol (tRes), a naturally occurring plant stilbenoid has been the focus of great attention because it is an efficacious antioxidant and anti-inflammatory agent with numerous potential therapeutic applications. Few natural compounds with such a broad spectrum of activities resulting from simultaneous interactions with multiple molecular targets and showing such impressive health benefits have been identified. Although initial pre-clinical studies are encouraging, the oral bioavailability of native, free tRes following rapid absorption is poor due to swift conjugation to glucuronides and sulfates. Additionally, tRes is a strong inhibitor of several important enzymes of the cytochrome P450 (CYP) system. The rapid metabolism of tRes generally is viewed as the critical barrier to clinical development of this potentially valuable therapeutic agent. Increasing the dose of tRes, however, may not be a good option to overcoming its limited bioavailability because this could lead to unpredictable drug interactions via alterations in CYP metabolism.
Because of the enormous therapeutic potential of tRes, there is a need for improved tRes analogs with increased bioavailability and longer half-lives. Such analogs or derivatives may have enhanced biological properties and, consequently, improved therapeutic efficacy. Similarly, there is a need for the identification of the molecular targets of tRes and its analogs because such information may lead to the design and development of improved therapeutic agents.